Open Label Extension Study Evaluating Safety and Tolerability of AAB-003 (PF-05236812) in Subject With Mild to Moderate Alzheimer's Disease

A Multicenter, Open-label Extension, Multiple Dose, Parallel Group Study To Investigate The Long-term Safety And Tolerability Of Aab-003 (Pf-05236812) Administered Intravenously In Subjects With Mild To Moderate Alzheimer's Disease Previously Treated With Aab-003 Or Placebo In Protocol B2601001

This is a study to evaluate the safety and tolerability of multiple doses of AAB-003 (PF-05236812) in patients with mild to moderate Alzheimer's Disease. Patients who complete study B2601001 may participate in this trial and receive AAB-003 (PF-05236812). Each patient's participation will last approximately 52 weeks.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: AAB-003 (PF-05236812); Drug: AAB-003 (PF-05236812); Drug: AAB-003 (PF-05236812); Drug: AAB-003 (PF-05236812); Drug: AAB-003 (PF-05236812)

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Incheon, Korea, Republic of, 400-711
    • Inha University Hospital, Department of Neurology
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center
  • Seoul, Korea, Republic of, 1350710
    • Samsung Medical Center, Department of Neurology
  • Seoul, Korea, Republic of, 136-705
    • Korea University Anam Hospital IRB
  • Seoul, Korea, Republic of, 143914
    • Konkuk University Medical Center, Department of Neurology
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 463-707
      • Seoul National University Hospital, Department Neurology
• United States
  • Florida
    • Hallandale Beach, Florida, United States, 33009
      • MD Clinical
    • Ocala, Florida, United States, 34471
      • Renstar Medical Research
    • Ocala, Florida, United States, 34471
      • Munroe Regional Medical Center
    • Ocala, Florida, United States, 34481
      • Advanced Imaging of Ocala
    • Ocala, Florida, United States, 34471
      • Trinity Care Solutions
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Atlanta Center for Medical Research
  • Maryland
    • Bethesda, Maryland, United States, 20814
      • Foers Medical Arts Pharmacy
    • Rockville, Maryland, United States, 20850
      • CBH Health, LLC
  • Michigan
    • Kalamazoo, Michigan, United States, 49048
      • Borgess Medical Center
    • Kalamazoo, Michigan, United States, 49048
      • Borgess Research Institute
    • Kalamazoo, Michigan, United States, 49048
      • KNI Southwest Michigan Imaging Center, LLC
  • Missouri
    • Creve Coeur, Missouri, United States, 63141
      • Millennium Psychiatric Associates, LLC
    • St. Louis, Missouri, United States, 63044
      • DePaul Health Center-MRI Department
  • New Jersey
    • Eatontown, New Jersey, United States, 07724
      • Memory Enhancement Center of America, Inc.
    • Oakhurst, New Jersey, United States, 07755
      • Central Jersey Radiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Successful completion of study B2601001
• MMSE 12 or greater

Exclusion Criteria:

• Study B2601001 Week 32 MRI with clinically important exclusionary findings.
• Experienced SAE, vasogenic edema and/or intracranial hemorrhage in study B2601001

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.5 mg/kg AAB-003	Drug: AAB-003 (PF-05236812); 0.5 mg/kg AAB-003, IV; Drug: AAB-003 (PF-05236812); 1 mg/kg AAB-003, IV; Drug: AAB-003 (PF-05236812); 2 mg/kg AAB-003, IV; Drug: AAB-003 (PF-05236812); 4 mg/kg AAB-003, IV; Drug: AAB-003 (PF-05236812); 8 mg/kg AAB-003, IV
Experimental: 1 mg/kg AAB-003	Drug: AAB-003 (PF-05236812); 0.5 mg/kg AAB-003, IV; Drug: AAB-003 (PF-05236812); 1 mg/kg AAB-003, IV; Drug: AAB-003 (PF-05236812); 2 mg/kg AAB-003, IV; Drug: AAB-003 (PF-05236812); 4 mg/kg AAB-003, IV; Drug: AAB-003 (PF-05236812); 8 mg/kg AAB-003, IV
Experimental: 2 mg/kg AAB-003	Drug: AAB-003 (PF-05236812); 0.5 mg/kg AAB-003, IV; Drug: AAB-003 (PF-05236812); 1 mg/kg AAB-003, IV; Drug: AAB-003 (PF-05236812); 2 mg/kg AAB-003, IV; Drug: AAB-003 (PF-05236812); 4 mg/kg AAB-003, IV; Drug: AAB-003 (PF-05236812); 8 mg/kg AAB-003, IV
Experimental: 4 mg/kg AAB-003	Drug: AAB-003 (PF-05236812); 0.5 mg/kg AAB-003, IV; Drug: AAB-003 (PF-05236812); 1 mg/kg AAB-003, IV; Drug: AAB-003 (PF-05236812); 2 mg/kg AAB-003, IV; Drug: AAB-003 (PF-05236812); 4 mg/kg AAB-003, IV; Drug: AAB-003 (PF-05236812); 8 mg/kg AAB-003, IV
Experimental: 8 mg/kg AAB-003	Drug: AAB-003 (PF-05236812); 0.5 mg/kg AAB-003, IV; Drug: AAB-003 (PF-05236812); 1 mg/kg AAB-003, IV; Drug: AAB-003 (PF-05236812); 2 mg/kg AAB-003, IV; Drug: AAB-003 (PF-05236812); 4 mg/kg AAB-003, IV; Drug: AAB-003 (PF-05236812); 8 mg/kg AAB-003, IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-SAEs.	Baseline up to Week 52
Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern	The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell [RBC] count, RBC morphology, platelet count, white blood cell [WBC] count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen [BUN], creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin, alkaline phosphatase, uric acid, albumin, and total protein; urinalysis (pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, microscopy [if urine dipstick was positive for blood, protein, nitrites or leukocyte esterase]); others (coagulation panel, circulating immune complex, and complement activation).	Baseline up to Week 52
Number of Participants With Potentially Clinically Important Vital Sign Findings	Vital signs assessment included pulse rate and blood pressure. Criteria for vital sign values meeting potential clinical concern included: supine/sitting pulse rate <40 or >120 beats per minute (bpm); standing pulse rate <40 or >140 bpm; systolic blood pressure (SBP) of more than or equal to (>=)30 millimeters of mercury (mm Hg) change from baseline in same posture or SBP <90 mm Hg, diastolic blood pressure (DBP) >=20 mmHg change from baseline in same posture or DBP <50 mm Hg.	Baseline up to Week 52
Number of Participants With Potentially Clinically Important Electrocardiogram (ECG) Findings	ECG parameters included PR interval, QRS interval, and QT interval. Criteria for ECG changes meeting potential clinical concern included: PR interval >=300 milliseconds (msec) or >=25% increase when baseline is >200 msec and >=50% increase when baseline is less than or equal to (<=)200 msec; QRS interval >=200 msec or >=50% increase from baseline when baseline is less than or equal to 100 msec and >=25% increase when baseline is >100 msec; and QTcF >=450 msec or >=30 msec increase.	Baseline up to Week 52
Number of Participants With Abnormal Physical Examination Findings	A full physical examination consisted of an examination of the abdomen, genitourinary and cardiovascular systems, lungs, lymph nodes, mouth, musculoskeletal and neurological systems, skin, extremities, head, ears, eyes, nose, throat and thyroid gland. Criteria for abnormal physical findings was based on the investigator's discretion and any new physical examination findings were documented as AEs. Only sites with at least 1 participant abnormality are reported.	Baseline up to Week 52
Number of Participants With Abnormal Neurological Examination Findings	Neurological examinations were done to the extent needed to assess the subject for any potential changes in neurological status, as determined by the investigator. Examinations included level of consciousness, speech, cranial nerves, motor, sensory, coordination, gait, and tendon reflexes. Only tests with at least 1 participant abnormality are reported.	Baseline up to Week 52
Number of Participants With Suicidal Ideation or Suicidal Behavior as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)	The C-SSRS captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. C-SSRS assesses whether participant experienced the following: completed suicide; suicide attempt; preparatory acts towards imminent suicidal behavior; suicidal ideation; self-injurious behavior, no suicidal intent. The results presented are the number of participants with completed suicide or non-fatal suicide events or behaviors. Worsening of suicidal ideation was an increase in severity of suicidal ideation from baseline.	Baseline up to Week 52
Number of Participants With Any New Magnetic Resonance Imaging (MRI) Findings	Brain MRIs were collected to assess for potential drug-related changes that might have constituted a safety concern. Findings suggestive of either vasogenic edema or intracranial hemorrhage were to be reported as AEs of special circumstance.	Baseline up to Week 52

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer	Number of participants with positive sample(s) in the ADA assay and in the neutralizing anti-drug antibodies (NAb) assay. An endpoint titer >=6.64 corresponded to positive ADA category value. The number of participants who tested positive on 1 or more occasions is reported.	Baseline, Week 52
Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Scores at Week 52	ADAS-Cog is a structured scale that evaluates memory, orientation, attention, reasoning, language and constructional praxis. The ADAS-Cog comprises 11 items that are summed to a total score ranging from 0 to 70, with higher scores indicate greater cognitive impairment.	Baseline, Week 52
Change From Baseline in Disability Assessment in Dementia (DAD) at Week 52	The DAD is a functional assessment comprised of 40 items (17 items related to self-care and 23 items involving instrumental activities of daily living). The DAD assessment is scored from 0 to 100; higher scores indicate better function.	Baseline, Week 52
Change From Baseline in Neuropsychiatric Inventory (NPI) Behavioral Symptoms at Week 52	The NPI is an instrument used to assess changes of behavior that have appeared in a defined period of time in subjects with Alzheimer's Disease and other dementias. Twelve behavioral areas are assessed: delusions, apathy, hallucinations, disinhibition, agitation, irritability, depression, aberrant motor behavior, anxiety, nighttime behaviors, euphoria, appetite, and eating changes. The NPI score is based on frequency and severity of specific behaviors within these categories. Severity (1=Mild to 3=Severe), frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency*severity=each domain score (range 0-12). Total score=sum of each domain score (range 0-144); higher score=greater behavioral disturbances; negative change score from baseline=improvement.	Baseline, Week 52
Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) Scores at Week 52	The CDR scale is a dementia staging instrument that tracks the progression of cognitive impairment in the following 6 categories: memory, orientation, judgment and problem solving, involvement in community affairs, home and hobbies, and personal care. The CDR-SB scale is obtained by summing the ratings in each of the 6 categories, ranging from 0 to 18. Higher scores indicate greater disease severity.	Baseline, Week 52
Change From Baseline in Mini-Mental State Exam (MMSE) Scores at Week 52	The MMSE is a brief 30-point questionnaire test that is used to assess cognition. Scores range from 0 to 30, with higher scores indicating better cognitive state.	Baseline, Week 52

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: JANSSEN Alzheimer Immunotherapy Research & Development, LLC

Publications and helpful links

General Publications

• Delnomdedieu M, Duvvuri S, Li DJ, Atassi N, Lu M, Brashear HR, Liu E, Ness S, Kupiec JW. First-In-Human safety and long-term exposure data for AAB-003 (PF-05236812) and biomarkers after intravenous infusions of escalating doses in patients with mild to moderate Alzheimer's disease. Alzheimers Res Ther. 2016 Mar 1;8(1):12. doi: 10.1186/s13195-016-0177-y.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: May 10, 2011
• First Submitted That Met QC Criteria: June 7, 2011
• First Posted (Estimate): June 8, 2011

Study Record Updates

• Last Update Posted (Actual): March 10, 2017
• Last Update Submitted That Met QC Criteria: January 19, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Randomized; Safety Study; Open Label
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: B2601003